The overarching aim of this proposed project is to develop, optimize and quantitatively evaluate magnetic resonance imaging (MRI) methods for evaluating the biomechanical properties of bone. The current standard diagnostic of bone health, dual-energy X-ray absorptiometry (DXA), provides an approximate measure of bone mineral density, but it is a projection method that does not incorporate the full contribution of macro-structure, micro-architecture, collagen, or porosity to fracture resistance. Quantitative computed tomography (qCT) is able to partially circumvent these shortcomings of DXA, but remains limited in that it, and other X-ray based methods, are sensitive only to the mineral content of bone, which accounts for only ~~40% of bone by volume. Recent studies have shown that [1]H nuclear magnetic resonance (NMR) can discern multiple soft- tissue components of bone, including collagen, collagen-bound water, and pore water. Further, in cadaveric cortical bone samples, these NMR measures were found to better predict several mechanical properties related to bone fracture risk than current high resolution qCT. This project seeks to translate these [1]H NMR findings into clinical MRI methods for assessing whole bone fracture risk through three project aims. In Aim 1, [1]H NMR measurements from cortical bone samples will be used to design and test MRI methods for quantitatively measuring bound- and pore-water from bone. In Aim 2, these MRI methods, along with DXA and qCT, will be applied to multiple cadaveric bone sites (including the femoral neck and distal radius). The resulting MRI measures of bound-water, pore-water, and cross-sectional moment of inertia will be correlated with whole bone fracture resistance properties measured from the same sites and a lumbar vertebra. Similar correlations will be made between DXA and qCT measures for comparison. In Aim 3, the MRI methods will be translated to a human MRI system where they will be re-optimized for 3T (c/w 4.7T) and quantitatively evaluated for use at multiple anatomical sites (e.g., distal tibia femoral neck, ...). Ultimately, this project will result in MRI methods with the potential for improved clinical diagnostic evaluation of fracture risk and novel imaging biomarkers for the study bone disease and pharmacological treatment response.